A novel bicyclic enzyme inhibitor as a consensus peptidomimetic for the receptor-bound conformations of 12 peptidic inhibitors of HIV-1 protease

Journal of the American Chemical Society

Volumn 118, Issue 36, 1996, Pages 8511-8517

  Reid, Robert C ^a   March, Darren R ^a   Dooley, Michael J ^a   Bergman, Doug A ^a   Abbenante, Giovanni ^a   Fairlie, David P ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; MACROCYCLIC COMPOUND; PROTEINASE INHIBITOR;

ARTICLE; DRUG DESIGN; DRUG STABILITY; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME BINDING; ENZYME INHIBITION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; MOLECULAR DYNAMICS; NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION; X RAY CRYSTALLOGRAPHY;

EID: 0029819214     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja960433v     Document Type: Article

References (31)

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8. X-ray crystal structure of 1 (pdb accession code : laaq): Dreyer, G. B.; Lambert, D. M.; Meek, T. D.; Carr, T. J.; Tomaszek, T. A.; Fernandez, A. V.; Bartus, H.; Cacciavillani, E.; Hassel, A. M.; Minnich, M.; Petteway, S. R.; Metcalf, B. W. Biochemistry 1992, 31, 6646.
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11. X-ray crystal structure of 4 (pdb accession code : 1hvi) and of 9 (pdb accession code : 1hvj): Hosur, M. V.; Bhat, T. N.; Kempf, D.; Baldwin, E. T.; Liu, B.; Gulnik, S.; Wideburg, N. E.; Norbeck, D. W.; Appelt, K.; Erickson, J. W. J. Am. Chem. Soc. 1994, 116, 847.
12. X-ray crystal structure of 5 (pdb accession code : 4hvp): Miller, M.; Schneider, J.; Sathyanarayane, B. K.; Toth, M. V.; Marshall, G. R.; Clawson, L.; Salk, L.; Kent, S. B. H.; Wlodawer, A. Science 1989, 246, 1149.
13. X-ray crystal structure of 6 (pdb accession code : 8hvp): Jaskolski, M.; Tomaselli, A. G.; Sawyer, T. K.; Staples, D. G.; Heinrikson, R. L.; Schneider, J.; Kent, S. B. H.; Wlodawer, A. Biochemistry 1991, 30, 1600.
14. X-ray crystal structure of 7 (pdb accession code : 9hvp): Erickson, J.; Neidhart, D. J.; Van Drie, J.; Kempf, D. J.; Wang, X. C.; Norbeck, D. W.; Plattner, J. J.; Rittenhouse, J. W.; Turon, M.; Wideburg, N.; Kohlbrenner, W. E.; Simer, R.; Welfrich, R.; Paul, D. A.; Knigge, M. Science 1990, 249, 527.
15. X-ray crystal structure of 8 (pdb accession code : 1hps): Thompson, S. K.; Murthy, K. H. M.; Zhao, B.; Winborne, E.; Green, D. W.; Fisher, S.; DesJarlais, R. L.; Tomasek, T. A.; Meek, T. D.; Gleeson, J. G.; Abdel-Meguid, S. S. To be published.
16. X-ray crystal structure of 10 (pdb accession code : 4phv): Bone, R.; Vacca, J. P.; Anderson, P. S.; Holloway, M. K. J. Am. Chem. Soc. 1991, 113, 9382.
17. X-ray crystal structure of 11 (pdb accession code : 1sbg): Abdet Meguid, S. S.; Metcalf, B. W.; Carr, S. T. J.; Demarsh, P.; DesJarlais, R. L.; Fisher, S.; Green, D. A.; Ivonoff, L.; Lambert, D. M.; Murthy, K. H. M.; Petteway, S. R.; Pitts, W. J.; Tomasek, T. A.; Winborne, E.; Zhao, B.; Dreyer. G. B.; Meek, T. D. To be published.
18. X-ray crystal structure of 12 (pdb accession code : 7hvp): Swain, A.; Miller, M. M.; Green, J.; Rich, D. H.; Schneider, J.; Kent, S. B. H.; Wlodawer, A. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 8805-8809.
19. (a) Epoxides: Rich, D. H.; Sun, C.-Q.; Prasad, J. V. N. V.; Pathiasseril, A.; Toth, M. V.; Marshall, G. R.; Clare, M.; Mueller, R. A.; Houseman, K. J. Med. Chem. 1991, 34, 1222-1225.
20. (b) The synthesis of 14 (shown in Scheme 1, supporting information) and the S-diasteromer of 13 are described in detail elsewhere: Reid, R. C. et al Submitted for publication.
21. Abbenante, G.; March, D. R.; Bergman, D. A.; Hunt, P. A.; Garnham, B.; Dancer, R. J.; Martin, J. L.; Fairlie, D. P. J. Am. Chem. Soc. 1995, 117, 10220-10226.
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23. Insight 2.3.5 and Discover 2.9.6 (Biosym Technologies, San Diego) were used on a Silcon Graphics Extreme work station.
24. Enzyme/assay references: (a) Schneider, J.; Kent, S. B. H. Cell 1988, 54, 363-8. (b) Wlodawer, A.; Miller, M.; Jaskólski, M.; Sathyanarayana, B. K.; Baldwin, E.; Weber, I. T.; Selk, L. M.; Clawson, L.; Schneider, J., Kent, S. B. H.Science 1989, 245, 616-621. (c) Bergman, D. A.; Alewood, D.; Alewood, P. F.; Andrews, J. L.; Brinkworth, R. I.; Engelbretsen, D. R.; Kent, S. B. H. Lett. Peptide Sci. 1995, 2, 99-107.
25. Enzyme/assay references: (a) Schneider, J.; Kent, S. B. H. Cell 1988, 54, 363-8. (b) Wlodawer, A.; Miller, M.; Jaskólski, M.; Sathyanarayana, B. K.; Baldwin, E.; Weber, I. T.; Selk, L. M.; Clawson, L.; Schneider, J., Kent, S. B. H.Science 1989, 245, 616-621. (c) Bergman, D. A.; Alewood, D.; Alewood, P. F.; Andrews, J. L.; Brinkworth, R. I.; Engelbretsen, D. R.; Kent, S. B. H. Lett. Peptide Sci. 1995, 2, 99-107.
26. Enzyme/assay references: (a) Schneider, J.; Kent, S. B. H. Cell 1988, 54, 363-8. (b) Wlodawer, A.; Miller, M.; Jaskólski, M.; Sathyanarayana, B. K.; Baldwin, E.; Weber, I. T.; Selk, L. M.; Clawson, L.; Schneider, J., Kent, S. B. H.Science 1989, 245, 616-621. (c) Bergman, D. A.; Alewood, D.; Alewood, P. F.; Andrews, J. L.; Brinkworth, R. I.; Engelbretsen, D. R.; Kent, S. B. H. Lett. Peptide Sci. 1995, 2, 99-107.
27. Passmore, M. et al Unpublished work. Detailed analyses of these and other cycles will be reported separately in the context of structure-activity relationships and pharmacological properties of macrocyclic inhibitors of HIV-1 protease.
28. (o/w) = 2.7 for 13, calculated using PALLAS pKalc and PrologP available from Compudrug Chemistry Ltd, Hungary.
29. 50 ∼ 110 nM) when exposed for 4 days to PHA-stimulated cord blood mononuclear cells infected with HIV-1 (strain TC354). Inhibition of HIV replication was determined by RT activity, assessed 4 days post inoculation.
30. Lam, P. Y. S.; Jadhav, P. K.; Eyermann, C. J.; Hodge, C. N.; Ru, Y.; Bacheler, L. T.; Meek, J. L.; Otto, M. J.; Rayner, M. M.; Wong, Y. N.; Chang, C.-H.; Weber, P. C.; Jackson, D. A.; Sharpe, T. R.; Erickson-Viitanen, S. Science 1994, 263, 380-384.
31. Fairlie, D. P.; Abbenante, G.; March, D. R. Curr. Med. Chem. 1995, 2, 672-705 and references therein.